Interest in global health among applicants to medical schools, residency programs, and infectious disease fellowships has grown enormously in recent years, but the career development pathways for translating this interest into successful academic careers remain poorly defined and perilous, with relatively few mentors available in academia. The candidate for this K24 Award is an Associate Professor of Pediatrics and Medicine who has established a funded research program to investigate the immune response to childhood malaria and identify in vitro correlates of protective immunity among children in high transmission settings. This research program is based upon strong collaborative relationships with leading malaria epidemiologists and clinical trialists working in Uganda. The PI and her collaborators have forged an effective multidisciplinary team and have built substantial research infrastructure to conduct field studies in Tororo, Uganda, a setting of exceptionally high malaria transmission intensity. Malaria is the leading cause of pediatric deaths in Uganda and claims the life of more than one million children worldwide each year. The need for an effective vaccine against malaria is self-evident. However the iterative process of vaccine development, refinement, and testing would be greatly aided by a better understanding of the immunologic effector mechanisms that confer protection from malaria, as well as immune subversion mechanisms that may hinder the development of durable immunity. Our current understanding of the mechanisms of immune protection from malaria is very limited, and comes mostly from experimental vaccination studies of animals and humans. To date, population-based studies of the malaria-specific T cell response among children naturally exposed to malaria have been few in number and limited by shortcomings in study design. The proposed studies will use samples obtained from well-characterized pediatric cohorts to identify correlates of protective immunity to malaria, and to determine how the natural acquisition of antimalarial immunity is altered by chemopreventive interventions and by prenatal exposure to malaria and to HIV. In addition, this award will enable the candidate to branch into new areas of investigation including the role of semi-innate ?? T cells in malaria infection and clinical tolerance. The primary goal of this K24 will be to develop a cohort of young investigators with the skills require to conduct high quality translational immunology research, encourage their passion for patient-oriented global health research, and help them to become successful independent investigators. Trainees will include U.S. physician scientists at all levels - infectious disease fellows, post-doctoral scholars, residents, and students - working side by side with Ugandan scientists and students to conduct innovative immunology research in a region of exceptionally high malaria transmission intensity, while capacitating U.S. and Ugandan researchers to work in collaborative teams.